PURPOSE OF REVIEW: This review aimed to highlight the known role of histone deacetylases (HDACs) and lysine acetyltransferases (KATs) in individuals with obesity, better understand the role of HDACs and KATs enzymes in obesity and related metabolic disorders. RECENT FINDINGS: Numerous cellular activities, including DNA replication, DNA repair, cell cycle regulation, RNA splicing, signal transmission, metabolic function, protein stability, transportation, and transcriptional regulation, are influenced by lysine acetylation. Protein lysine acetylation serves several purposes, which not only contribute to the development of metabolic disorders linked to obesity but also hold promise for therapeutic approaches. The current study demonstrates that HDACs and KATs control lysine acetylation. This review details the advancements made in the study of obesity, related metabolic diseases, and protein lysine acetylation. It contributes to our understanding of the function and mechanism of protein lysine acetylation in obesity and MS and offers a fresh method for treating these diseases.